Apr 26, 2010 by Emily Caldwell

A new study links progression of a lethal type of brain tumor with reduced expression of more than 600 immune system genes, suggesting how complex the immune response is to the cancer and the resulting difficulty in targeting specific immune system proteins for treatment.

Previous research found that people with allergies were less likely to be diagnosed with this type of brain cancer, called glioblastoma multiforme. However, it was not clear whether allergies reduce brain tumor risk or whether the growing tumor "cures" allergies.

To further explore the relationship between these two conditions, scientists examined almost 1,000 genes associated with allergies, immunity and inflammation to learn how they were affected once these tumors were present in the brain.

The researchers expected to see that allergy gene function was low in brain tumor tissue, which would be consistent with the known immune system suppression that is associated with these tumors.

What they found was a surprise: Allergy genes were not the only immune function genes suppressed during tumor growth. Instead, in almost 70 percent of the 919 genes examined, the genes' activity was decreased as the brain tumors progressed.

"This result provides evidence that there is a relationship between glioblastoma and allergies - specifically, high tumor aggressiveness is associated with low allergy-related gene function," said Judith Schwartzbaum, lead author of the study and an associate professor of epidemiology at Ohio State University. "But it still does not tell us whether allergies inhibit tumor growth or tumors block allergies."

The findings also show that immune function in the brain continues to change as these tumors grow.

"As the tumor progresses, the majority of the immune-function genes express themselves at lower levels," Schwartzbaum said. "So we know that with progression there is less immune function, but we don't know which came first, the lowered immune function or the cancer."

The cause of this kind of cancer remains unknown, and there is no cure. The complexity of the immune response to this tumor suggests that it will be difficult to identify key immune function proteins that inhibit tumor growth. Schwartzbaum said that in addition to using information about the immune system to treat tumors, researchers must also study the immune system to find ways to prevent these aggressive tumors.

The study is published in a recent issue of the journal Neuro-Oncology.

Glioblastomas constitute up to 60 percent of adult primary brain tumors in the United States, affecting an estimated 3 in 100,000 people. Patients who undergo surgery, radiation and chemotherapy survive on average for about one year, with fewer than a quarter of patients surviving up to two years and fewer than 10 percent surviving up to five years.

The researchers used publicly available data from genetic analysis of 142 brain tumor tissue samples collected from patients with glioblastoma multiforme tumors as part of the National Cancer Institute's The Cancer Genome Atlas project.

The scientists used levels of expression of the CD133 gene as an indicator of tumor progression. Previous studies had suggested that activation of this gene is related to tumor aggression and a poor clinical outcome.

With these data, Schwartzbaum and colleagues then plotted expression of immune function genes against levels of CD133 expression in these tumors.

Gene expression refers to the switching on or activation of genes. Schwartzbaum and her colleagues analyzed mRNA expression data in their study; mRNA synthesis is the first step in gene expression and may lead to creation of functional proteins.

The analysis showed that higher levels of CD133 expression were associated with lower levels of immune function gene expression in 69 percent of the genes examined.

There were, however, immune function genes whose expression increased with CD133 expression, including a cytokine gene called interleukin-17 that is linked to inflammation, and a gene related to suppression of immune function called NCAM-1.

The genes whose function was lowered with tumor progression included most of those associated with allergies, as well as, paradoxically, many of those that counteract allergy genes. In another surprising finding, many genes known to suppress immune function were also expressed at lower levels as the tumor progressed.

"That was a surprise because you'd think that genes that suppress the immune system would be more active in these tumors, which may be lethal, in part, because they are immunosuppressive. But we didn't see that," Schwartzbaum said.

Schwartzbaum is planning to focus her subsequent research on the end products of genetic activation, immune function proteins or cytokines.

She plans to analyze 1,200 samples from the Janus Serum Bank in Norway, which were collected on average 10 years before brain tumor diagnosis, to find out whether the presence of certain cytokines in those samples might offer clues that will help identify people at high risk for brain tumor development.

Related Stories

One of the fundamental traits of a tumor – how it avoids the immune system – might become its greatest vulnerability, according to researchers from the University of Southern California. Their findings, demonstrated ...

Massachusetts General Hospital (MGH) researchers are investigating a new approach to gene therapy for brain tumors – delivering a cancer-fighting gene to normal brain tissue around the tumor to keep it from spreading. ...

Doctors diagnose and prescribe treatment for brain tumors by studying, under a microscope, tumor tissue and cell samples obtained through invasive biopsy or surgery. Now, researchers at UCSD School of Medicine have shown ...

People with a particular gene variant may be more likely to develop brain tumors, and at an earlier age, than people without the gene, according to a study published in the January 27, 2009, print issue of Neurology, the me ...

Findings from a study conducted in mice, published in the open access journal PLoS Medicine next week, provide new insights into how an effective immune response to brain tumors could potentially be brought about in humans ...

After five years of follow-up, a majority of asymptomatic, benign thyroid nodules exhibited no significant change in size, or actually decreased in size, and diagnoses of thyroid cancer were rare, according to a study in ...

Tumor recurrence following a period of remission is the main cause of death in cancer. The ability of cancer cells to remain dormant during and following therapy, only to be reactivated at a later time, frequently ...

Extra virgin olive oil (EVOO), long-known for its heart health benefits, has now been identified for its rapid destruction of cancer cells. While scientists have proven that the oleocanthal compound found ...

A magnetic resonance spectroscopy (MRS) technique that monitors biochemical changes in tissue could improve the management of women at risk of breast cancer, according to a new study published online in the ...

Despite sharp increases in spending on cancer treatment, cancer mortality rates in the United States have decreased only modestly since 1970, Samir Soneji, PhD of Dartmouth's Norris Cotton Cancer Center and The Dartmouth ...

User comments : 0

Please sign in to add a comment.
Registration is free, and takes less than a minute.
Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.

Javascript is currently disabled in your web browser. For full site functionality, it is necessary to enable Javascript.
In order to enable it, please see these instructions.